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Biomedical subjects

J E Scott

Publications and source records attributed to J E Scott.

At least 145 records · Page 8Linked to original sources

Ehrlich chromogens, probable cross-links in elastin and collagen.

(1) Proteolytic digests of tissue elastin contain material which reacts with dimethylaminobenzaldehyde in acid solution (Ehrlich's reagent) to give a cherry-pink colour. This Ehrlich chromogen(s) [EC(s)] is similar to but not identical with EC(s) previously demonstrated in tissue collagens [Scott, Hughes & Shuttleworth (1979) Biosci. Rep. 1, 611-618]. Both ECs react with diazonium salts in acid to give coloured products. (2) Diazobenzene linked via a phenolic ester to polyacrylamide beads (Biogel P10) has been used to absorb ECs specifically and almost quantitatively from proteolytic digests. The coupled deeply coloured azo-EC-peptides were then recovered after mild alkaline cleavage from the support and purified by gel chromatography. (3) Using 15N-labelled NaNO2, the collagen azo-EC-peptides were prepared, and 15N abundance measured therein. The molar absorption coefficient of the azo-EC group was calculated (18,700) based on the assumption that each azo-EC group contained one 15N atom. (4) Collagen azo-EC-peptides contained glucose and galactose, whereas elastin azo-EC peptides did not. The amino acid patterns of the two peptides were quite different, the former being rich in polar amino acids, the latter containing much alanine. The patterns were compatible with an origin from the cross-linking regions of collagen and elastin respectively. (5) Quantitative (molar) comparisons of the azo-EC group content with amino acid, amino end-group and sugar contents, and azo-EC peptide molecular mass, suggest that a structure is present in the collagen azo-EC-peptides containing two EC groups shared between four peptide chains. Three peptide chains probably meet at each (cross-linking) EC group. (6) Based on this structure, about 15% of adult bovine skin collagen contains EC groups.

Amino Acids↗

Beta-adrenergic-induced surfactant synthesis, secretion, and reutilization in fetal rabbit lung and isolated differentiating type II alveolar cells.

In vivo and in vitro approaches were used to examine the role of beta-adrenergic agonists in the regulation of surfactant synthesis and secretion in the lung. Rabbit fetuses of either 28 or 30 gestational days were treated with isoxsuprine. Fetuses from half of the does in each group were removed and allowed to breathe for 30 minutes. The others were left in utero. Intracellular and extracellular surfactant pools were isolated. Breathing increased secreted surfactant. On the twenty-eighth day without breathing, isoxsuprine treatment increased secretion of surfactant. The reverse effect was noted in the group that received the drug and also breathed. In contrast, on the thirtieth day, the drug inhibited surfactant release in those fetuses that did not breathe. In in vitro studies, undifferentiated type II alveolar cells were isolated and stimulated to differentiate. Subsequent exposure to isoxsuprine (5 or 10 mumol/L) stimulated both the synthesis and secretion of radiolabeled disaturated phosphatidylcholine. Concurrent incubation of those cells exposed to 10 mumol/L isoxsuprine with either unsaturated or disaturated phosphatidylcholine that was carbon 14 labeled showed a strong preference for incorporation of the latter phospholipid into total cellular phosphatidylcholine. These results suggest that beta-adrenergics may inhibit as well as stimulate secretion of surfactant by type II alveolar cells and that these cells may reincorporate secreted disaturated phospholipid.

Adrenergic beta-Agonists↗

Pulmonary toxicity of trichloroethylene: induction of changes in surfactant phospholipids and phospholipase A2 activity in the mouse lung.

Trichloroethylene (TCE) is a common organic solvent in use as a dry cleaning agent as well as an inhalant anesthetic. Nevertheless the effects of this material on the pulmonary surfactant which prevents alveolar collapse at maximal expiration is not known. Therefore, we have examined the effect of TCE on the intra- and extracellular surfactant pools and the activity of phospholipase A2, an enzyme which controls the remodeling of phosphatidylcholine to dipalmitoylphosphatidylcholine, the primary constituent of the pulmonary surfactant. Male CD-1 mice were treated ip with 2500 or 3000 mg/kg TCE. Twenty-four hours later mice were anesthetized and the lungs lavaged. Mice were then killed, the lungs perfused and excised, and subcellular fractions including lamellar bodies prepared. Some lungs were prepared for ultrastructural examination. Phospholipase A2 was assayed in all subcellular fractions. Phospholipid was assayed in the lavage (extracellular surfactant) and the lamellar bodies (intracellular surfactant). TCE (2500 mg/kg) caused selective exfoliation of Clara cells. However, only the dose of 3000 mg/kg TCE produced a significant decrease in the intracellular surfactant phospholipid. Minimal changes occurred in the phospholipid profiles. Phospholipase A2 specific activity was significantly decreased at both dosages within the lung microsomal fraction. In addition after treatment with 3000 mg/kg TCE the enzyme activity in the lamellar body fraction was significantly increased. These data suggest that inhalation of TCE may damage the enzymes which are responsible for synthesizing the pulmonary surfactant resulting in lower amounts of surfactant being stored and available for secretion into the alveolus.

Animals↗

The complete DNA sequence of the long unique region in the genome of herpes simplex virus type 1.

We have determined the DNA sequence of the long unique region (UL) in the genome of herpes simplex virus type 1 (HSV-1) strain 17. The UL sequence contained 107,943 residues and had a base composition of 66.9% G + C. Together with our previous work, this completes the sequence of HSV-1 DNA, giving a total genome length of 152,260 residues of base composition 68.3% G + C. Genes in the UL region were located by the use of published mapping analyses, transcript structures and sequence data, and by examination of DNA sequence characteristics. Fifty-six genes were identified, accounting for most of the sequence. Some 28 of these are at present of unknown function. The gene layout for UL was found to be very similar to that for the corresponding part of the genome of varicella-zoster virus, the only other completely sequenced alphaherpesvirus, and the amino acid sequences of equivalent proteins showed a range of similarities. In the whole genome of HSV-1 we now recognize 72 genes which encode 70 distinct proteins.

Amino Acid Sequence↗

Antenatal diagnosis of congenital abnormalities in the urinary tract. Results from the Northern Region Fetal Abnormality Survey.

One hundred and sixty-two cases of suspected congenital abnormalities of the urinary tract notified to the Northern Region Fetal Abnormality Survey Register between the beginning of 1984 and the end of 1986 were studied. These cases represented 14.3% of total notifications, which in turn were 0.93% of total births. There were a further 25 cases notified but not due for delivery until early 1987; 10 of these were urological. Thirty-five cases (22%) notified proved postnatally to have normal urinary tracts and 21 (13.2%) had unsuspected urinary tract abnormalities. Of the 106 cases in which a suspected urinary tract abnormality was confirmed postnatally, confirmation was obtained at perinatal death in 32 and by ultrasound, radiographic and radioisotope investigation in the remainder; 34.5% of all urological cases registered and 75% of the confirmed survivors were treated surgically. The urological abnormality most frequently missed was posterior urethral valves. Attempts to diagnose the fetal sex were seldom made but when they were the prediction was usually male and usually correct. The perinatal mortality in this group was 0.43/1000 births, a contribution of nearly 4% to overall perinatal mortality in the Northern Region.

Female↗

Characterization and comparison of the role of beta-agonists on in vivo and in vitro surfactant-related phospholipid synthesis and secretion by fetal rabbit lung and isolated type II alveolar cells.

The role of beta-adrenergic stimulation in surfactant synthesis and secretion was investigated in the fetal lung. Fetuses were treated with isoxsuprine or saline on gestational day 24 by ip injection. Three days later the fetal lungs were lavaged and intracellular surfactant was isolated on a sucrose gradient. Concurrently undifferentiated type II alveolar cells were isolated from 24-day fetal rabbit lung and grown in vitro. In the in vivo portion of the study, examination of surfactant pool sizes revealed that only saline treatment produced a significant elevation in tissue-stored or secreted surfactant compared to untreated controls. Isoxsuprine appeared to inhibit the saline-induced increase. In the case of the intracellular surfactant, the phosphatidylcholine content per gram of lung was significantly increased after saline treatment. In vitro response of isolated type II alveolar cells to isoxsuprine was dependent on prior incubation of the cells for 24 h with conditioned medium. Isoxsuprine stimulated a dose-dependent decrease in the intracellular stores of radioactively labeled DSPC after 24 h of exposure to the drug. A corresponding increase in labeled DSPC in the culture medium was observed. Forth-eight hours after exposure to the drug, those cells that had secreted the highest level of DSPC displayed the highest levels of renewed synthesis of DSPC. This study indicates that the immature fetal lung can be induced to synthesize surfactant-related phospholipid by the stress of laparotomy and/or drug administration. Short-term exposure to beta-agonists is insufficient to stimulate secretion of surfactant stores. In contrast, isolated type II alveolar cells exposed to isoxsuprine respond by secreting DSPC.

Adrenergic beta-Agonists↗

Keratan sulphate and the ultrastructure of cornea and cartilage: a 'stand-in' for chondroitin sulphate in conditions of oxygen lack?

Corneas from mouse, rat and rabbit were analysed quantitatively and/or qualitatively for collagen and acid glycosaminoglycans. They were examined by light and electron microscopy, using Alcian blue and Cupromeronic blue, in critical electrolyte concentration methods, with or without digestion by hyaluronidase, chondroitinases and keratanase, for their sulphated glycosaminoglycan distributions. Glycosaminoglycan patterns were very different in the three species. Mouse lacked chemically detectable keratan sulphate, which was present in considerable amounts in rat and rabbit stroma. Mouse corneal stroma proteoglycan filaments were located predominantly at the gap zone of the collagen fibrils, mainly at the d band, with few at the a and c bands. Rat and rabbit micrographs were more complicated, with many proteoglycan filaments at the a and c, as well as the d and e bands. These findings support the proposal that the a and c bands were specific binding sites for keratan sulphate proteoglycan (Scott & Haigh, 1985b). Evidence from studies on cornea and cartilage suggests that keratan sulphate, rather than chondroitin sulphate is produced in conditions of O2 lack. Metabolic mechanisms which could account for this balance are proposed The production of uridine diphosphate glucuronic acid is the key step, which is sensitive to hypoxia, lactate and NAD:NADH ratios.

Animals↗

Profile of phospholipase A2 activity in subcellular fractions and lamellar bodies of developing, neonatal and adult rabbit lung. Correlation with intracellular levels of disaturated phosphatidylcholine.

Phospholipase A2 activity was determined in subcellular fractions and lamellar bodies of fetal, neonatal and adult rabbit lungs. Specific activity in most fractions decreased from the 24th to the 28th day of gestation. All fractions except the mitochondrial and the nuclear fractions exhibited a sharp increase in activity in the newborn lung. Specific activity in the adult lung generally declined in comparison to neonatal values. During gestation total enzyme activity per gram of lung was concentrated in the cytosolic fraction. With the exception of the lamellar body fraction, the total content of phospholipase A2 activity increased dramatically in all fractions from the neonatal lung. The lamellar body fractions displayed both low specific activity and low total enzyme activity during gestation. Specific activity increased dramatically in the neonatal and adult lung but still accounted for only a small fraction of the activity in comparison to the other subcellular fractions. The subcellular content of disaturated phosphatidylcholine (PC) appeared to correlate well with the activity of phospholipase A2 in the neonatal mitochondrial, microsomal and cytosolic fractions. Since decreasing prenatal enzyme levels are associated with increasing disaturated PC content, the alkaline and calcium-dependent phospholipase A2 may not be directly involved in disaturated PC synthesis in the fetus. However, postnatally, the correlation between the pattern of production of disaturated PC and the activity of the phospholipase A2 indicates a role for this enzyme in surfactant-related disaturated PC synthesis.

Animals↗

Dermatan sulphate proteoglycans from sclera examined by rotary shadowing and electron microscopy.

Two dermatan sulphate-containing proteoglycans from bovine sclera were examined by rotary shadowing and electron microscopy, and the results were compared with previous biochemical findings. Both the large iduronate-poor proteoglycan (PGI) and the small iduronate-rich proteoglycan (PGII) possessed a globular proteinaceous region. Whereas PGI had a branched extension from the globular region, with five to eight side chains attached to it, PGII had only a single tail, which was of glycosaminoglycuronan. PGII aggregated via globular-region interactions, which were much diminished by reduction and alkylation. PGI aggregated via side chains and globular-region interactions. Although a few PGI aggregates were large, and similar to the hyaluronan-cartilage proteoglycan aggregates [Weidemann, Paulsson, Timpl, Engel & Heinegård (1984) Biochem. J. 224, 331-333], hyaluronan did not cause enhanced aggregation. PGII is very similar in shape to the small cartilage chondroitin sulphate proteoglycan, whereas PGI somewhat resembles the large cartilage chondroitin sulphate proteoglycan, although with many fewer glycosaminoglycan side chains, and probably only one globular region as opposed to two in the cartilage proteoglycan.

Alkylation↗

Beta-glucuronidase activity is present in the microscopic epididymis of the Tfm/Y mouse.

The sex-linked recessive gene Tfm in the mouse produces a condition of testicular feminization (androgen insensitivity syndrome, AIS) in hemizygotes, comparable to the condition of the same name in humans. The murine mutant was originally believed to have no derivatives of the mesonephric duct system (MDS), and this absence was ascribed to dependence of these derivatives on androgens for survival. However, microscopical epididymides, retia testes, and vasa deferentia were identified in these animals in our laboratory. These micro-organs may play a role in meiosis induction in Tfm/Y animals. The present study was designed to determine whether survival of these organs is due to retention of an ability to respond to androgens, or whether they are unique amongst MDS derivatives in being independent of androgens. Previous studies in our laboratory demonstrated that the enzyme beta-glucuronidase (beta G) is androgen sensitive in the epididymis of the normal mouse. In the present investigation we used this enzyme as a marker to study androgen sensitivity in the microscopical epididymides of Tfm/Y hemizygotes and in the epididymides of control +/Y litter-mate brothers. Both mutant and control animals were studied with and without exogenous androgen stimulation. Tfm/Y hemizygotes demonstrated low levels of diffuse, cytoplasmic beta G activity that appears to be unresponsive to exogenous androgen stimulation. In light of our previous studies, this distribution of beta G reaction products suggests some degree of androgen sensitivity. The survival of these micro-organs and their partial androgen sensitivity may be related to the role of the MDS in inducing meiosis.

Androgen-Insensitivity Syndrome↗

Violence in Playboy magazine: a longitudinal analysis.

This paper analyzes the amount of violence in cartoons and pictorials from January 1954, through December 1983 in Playboy magazine. Inasmuch as the Attorney General's Commission on Pornography and Obscenity has focused upon magazines such as Playboy as potentially harmful to society because of the violence merged with sex, such an analysis is appropriate at this time. Each cartoon and pictorial for each issue of Playboy for the 30-year-period was examined for violent depictions. The average number of violent cartoons for the 30-year-period was 6.92/year or 0.58/issue. The average number of violent pictorials was less with an average of 1.89/year or 0.16/issue. The ratio of violent cartoons or pictorials to the total number of cartoons or pictorials was small. The ratio of violent cartoons to all cartoons was 25.2/1000 and for violent pictorials to all pictorials it was 8.6/1000. Moreover, the ratio of violent cartoons to total pages was 2.86/1000 and for violent pictorials 0.78/1000 pages. Although the overall number and ratio of violent cartoons and pictorials in Playboy over the 30-year-period examined was rare, a major question addressed was whether the amount of violence was increasing. Rather than a linear relation, a curvilinear relationship was observed with the amount of violence on the decrease in recent years. Although the effects of violence in sexual material is still being debated, those who argue for greater censorship of magazines such as Playboy because of its depictions of violence need a new rationale to justify their position.

Cartoons as Topic↗

Characterization and distribution of a phospholipase A2 activity from adult rabbit lung.

A phospholipase A2 activity was characterized in adult rabbit lung. This activity was calcium- and deoxycholate-dependent and displayed an alkaline pH optimum. Km and Vmax were 0.176 mM and 256.8 pmoles/min./mg protein respectively. The microsomal fraction displayed the highest enzymatic specific activity; the lowest activity was present in the cytosol. Yet this latter fraction accounted for the majority of the total activity. Although the specific activity was high within the lamellar body fraction this compartment contained only approximately 2% of the total activity. Phospholipase A2 activity was inhibited by bromophenacyl bromide, chlorpromazine and mepacrine in decreasing order of effectiveness. Treatment of the microsomes with increasing concentrations of NaC1 indicated that the lung phospholipase A2 activity was relatively loosely bound to the microsomal membranes and was maximally removed with salt at a concentration only slightly higher than physiological. Addition of calmodulin to the enzyme assay did not significantly alter hydrolysis of labelled phosphatidylcholine.

Animals↗

Utility of the health belief model in examining medication compliance among psychiatric outpatients.

This study investigates the relationship between health beliefs and medication compliance among a group of psychiatric outpatients who were prescribed antipsychotic drug regimens. The method of study was an interview with 107 outpatients discharged from two Veterans Administration Medical Centers. The health belief model (HBM) served as an organizing framework to explore the relationships among perceptions of illness severity, susceptibility, benefits and barriers of treatment, cues to action, and medication compliance. The results provide a systematic description of health beliefs reported by psychiatric outpatients. Analyses examine the ability of beliefs to predict compliance and affirm the model's theoretical cogency and appropriateness for use with psychiatric outpatients. Regression analysis showed that 20% of the total variance in compliance could be explained when all components of the HBM were examined together. The study supported the concepts that psychiatric outpatients hold identifiable patterns of health beliefs and attitudes and that the health belief framework functions best when utilized as an integrated model to examine compliance.

Adult↗

The Northern region Children's malignant disease registry 1968-82: incidence and survival.

All cases of childhood cancer diagnosed before the 15th birthday in the years 1968-1982 and resident in the Northern Health Authority region have been registered. There were 1171 registrations and only two have been completely lost to follow up. The overall annual incidence of cancer was 107.1 per million children, similar to previously reported figures. There was no significant change in the rate over the 15 year period either for all cancers or individual cancer types. Eighty six percent of registrations had central review of pathological material. There has been a significant move towards centralisation of care over the 15 years and a significant improvement in survival over the three quinquennia for all cases and for most individual types. High white blood cell count at presentation was confirmed as a bad prognostic feature in children with acute lymphoblastic leukaemia (ALL). Children treated for ALL in a peripheral hospital had a significantly worse survival than those referred to a specialist centre. Survival rates were calculated for all of the major types of malignancy. The registry includes four sibling pairs with cancer and one family with three siblings affected. Ten children developed secondary primary tumours.

Adolescent↗

The effect of muscle paralysis on the radial growth of collagen fibrils in developing tendon.

Voluntary muscle activity in chick embryos was paralysed by administration in ovo of tubocurarine hydrochloride, administered in single or multiple doses, from day 9 to day 13 after fertilization. Control eggs were given saline instead of tubocurarine or were simply incubated without operative interference. Embryos were killed at 9, 13, 14, 16 and 19 days after fertilization. Flexor digitorum tendons were removed, fixed in glutaraldehyde, embedded in plastic, sectioned, and stained with phosphotungstic acid for electron microscopy. The diameters of the tendon collagen fibrils were measured, on electron micrographs, using a Magiscan Mk II programme. Tendon collagen fibril expansion was not inhibited by tubocurarine treatment. It is concluded that the rapid increase of collagen fibril diameters, which coincides in the normal embryo with the first onset of use of the associated muscle, is not dependent on muscle activity. There remains a possibility that other ways of producing tension in the tendon could provide sufficient stimulus to fibril expansion.

Animals↗

Fetal ureteric reflux.

Seven babies (six male, one female) with ureteric reflux, all of whom had antenatal renal dilatation, are described together with one other baby who was found to have gross ureteric reflux when investigated following an acute urinary infection at the age of 9 days. There was a strong probability that all of the babies had fetal ureteric reflux (FUR). Radioisotope studies demonstrated parenchymal damage in three of seven and reduced function in four of 10 refluxing kidneys. Subsequent investigation showed no increase in the areas of parenchymal damage but there was evidence that function in some kidneys had deteriorated. It was thought that this was due to disturbances in inter-renal or renal-child related growth velocities. A plea is put forward for more detailed postnatal examination of babies whose urinary tracts show evidence of dilatation antenatally.

Dilatation, Pathologic↗

The Hutson hypothesis. A clinical study.

The hypothesis that testicular descent may be governed by Müllerian inhibiting substance (MIS) was investigated by observing the position of the testes in 13 children with XY karyotype and persistent Müllerian duct syndrome (PMDS). It was found that there was a direct relationship between failure of testicular descent and the degree of development of the Müllerian system. Where the Müllerian system was complete, the testes were in an ovarian position but where only the vagina was present, the testes were sometimes found in the inguinal region. To discover whether excessive androgen activity in females might produce ovarian descent, the position of the ovaries in 15 children with severe adrenogenital syndrome was observed. Despite complete genital masculinisation in three children and almost complete in six, all but one ovary was in the normal position: that ovary had descended in an inguinal hernia sac. These findings suggest that MIS rather than androgens may be responsible for the first or abdominal phase of testicular descent. Even excessive androgen activity failed to cause ovarian descent.

Adrenal Hyperplasia, Congenital↗

The role of sera, growth factors, and hormones in the in vitro production of disaturated phosphatidylcholine and propagation of undifferentiated type II alveolar cells from the fetal rabbit lung.

Undifferentiated type II alveolar cells isolated from the fetal rabbit lung were cultured in chemically-defined medium supplemented with 10% carbon-stripped fetal bovine serum for 2-3 days and then placed in serum-free medium, or medium supplemented with either 10% carbon-stripped fetal bovine serum (sFBS) or 10% unstripped fetal bovine serum. Cells exposed to the latter treatment showed the highest growth rate but the lowest level of [3H]choline incorporation into disaturated phosphatidylcholine (DSPC). Cells in serum-free medium showed the lowest rate of growth but removal of serum components stimulated a rapid increase in radioactive precursor incorporation. Cells exposed to the stripped serum were intermediate in both measurements. Incubation of undifferentiated type II cells with EGF stimulated growth but only in the presence of sFBS. EGF also stimulated [3H]choline into DSPC after 48 hours of exposure to the peptide. This latter response could only be elicited in serum-free medium. In the presence of sFBS no effect of the peptide was detected on radioactive precursor incorporation. Similarly dexamethasone (0.55 nM) or 20% medium which had been conditioned by fetal lung fibroblast monolayers did not stimulate [3H]choline in DSPC in the presence of sFBS. In contrast these agents did evoke a significant increase in radioactive precursor incorporation when the undifferentiated type II alveolar cells were incubated in serum-free medium.

Animals↗